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Connolly Hospital Dublin
St. Luke’s Radiation Oncology Network Dublin (5)
Author
Crown, John
(3)
Franicis, Prudence
(1)
Power, Richard E
(1)
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BACKGROUND: No proven targeted therapy is currently available for the treatment of triple-negative breast cancer (TNBC). Epidermal growth factor receptor (EGFR) is frequently overexpressed in TNBC. We studied the activity of EGFR antagonists alone, and in combination with chemotherapy, in TNBC cell lines. MATERIALS AND METHODS: EGFR and phosphorylated EGFR were measured by enzyme-linked immunosorbent assay. Sensitivity to EGFR inhibitors alone and in combination with chemotherapy was assessed. Effects of gefitinib on EGFR signalling and cell cycle were also examined. RESULTS: EGFR was overexpressed in the TNBC compared with the human epidermal growth factor receptor 2 (HER-2)-positive cell lines. Phosphorylation of EGFR was detected in the TNBC cells in response to epidermal growth factor stimulation and was blocked by gefitinib treatment. However, the TNBC cell lines were less sensitive to EGFR inhibition than the HER-2-positive cell lines. Response to gefitinib was associated with reduced phosphorylation of both mitogen activated protein kinase (MAPK) and Akt and induction of G(1) arrest. Gefitinib enhanced response to both carboplatin and docetaxel in the TNBC cells, and the triple combination of gefitinib, carboplatin and docetaxel was synergistic. CONCLUSIONS: Although the TNBC cells are less sensitive to EGFR inhibition than the HER-2-positive cell lines, gefitinib enhanced response to chemotherapy. Gefitinib combined with carboplatin and docetaxel warrants further investigation in TNBC (1)
BACKGROUND: The present approach to cancer treatment is often referred to as inappropriate therapy and treatment-related toxicity. In contrast, personalized treatment has the potential to increase efficacy and decrease toxicity. CONTENT: We reviewed the literature relevant to prognostic, predictive, and toxicity-related markers in cancer, with particular attention to systematic reviews, prospective randomized trials, and guidelines issued by expert panels. To achieve personalized treatment for cancer, we need markers for determining prognosis, predicting response to therapy, and predicting severe toxicity related to treatment. Among the best-validated prognostic markers currently available are serum concentrations of alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and lactate dehydrogenase (LDH) for patients with nonseminoma germ cell tumors and tissue concentrations of both urokinase plasminogen activator and plasminogen activator inhibitor 1 (PAI-1) for breast cancer patients. Clinically useful therapy predictive markers are estrogen and progesterone receptors to select patients with breast cancer for treatment with endocrine therapy and human epidermal growth factor receptor 2 (HER-2) to select breast cancer patients for treatment with trastuzumab (Herceptin). Markers available for identifying drug-induced adverse reactions include thiopurine methyltransferase (TPMT) to predict toxicity from thiopurines in the treatment of acute lymphoblastic leukemia and uridine diphosphate glucuronyltransferase to predict toxicity from irinotecan in the treatment of colorectal cancer (1)
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1)
MDR1/P-glycoprotein and MRP-1 Drug Efflux Pumps in Pancreatic Carcinoma
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Crown, John
Pub. Date
2007
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Epidermal growth factor receptor as a potential therapeutic target in triple-negative breast cancer
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Crown, John
Pub. Date
2009
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A personalized approach to cancer treatment: how biomarkers can help
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Crown, John
Pub. Date
2008
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4)
Pelvic recurrence in stage I seminoma: a new phenomenon that questions modern protocols for radiotherapy and follow-up
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Power, Richard E
Pub. Date
2005
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Adjuvent chemotherapy with sequential or concurrent anthracycline and docetaxel: breast international group 02-98 radomized trial
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Franicis, Prudence
Pub. Date
2008
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